Metabolism of Progesterone4-Cl4 and Pregnenolone-?a-H3 by Human Adrenal Tissue FORMATION OF 16cr-HYDROXYPROGESTERONE-C14, CORTICOSTEROn-E-C14, AND CORTISOL-Ci4-H3* IRVING WELIKY~. AND LEWIS L. ENGELS

The concept that cortisolr may be formed by more than one pathway, and pertinent literature leading to this concept, have been discussed previously in reference to the extensive conversion of 17-hydroxypregnenolone to cortisol by slices of a human adrenal cortical tumor (2). Villee et al. (3) demonstrated the conversion of progesterone to 16ac-hydroxyprogesterone (Reaction g, Fig. 1) by homogenates of human hyperplastic adrenal cortical tissue. It has been reported (4) that no significant conversion of pregnenolone to progesterone could be demonstrated in fetal adrenals and that 16a-hydroxypregnenolone was a quantitatively important metabolite of pregnenolone in the newborn anencephalic. These data support earlier data (5) that indicated a deficiency of As-3/3hydroxysteroid dehydrogenase or As-3-ketosteroid isomerase or both in the human fetal adrenal. Fukushima, Smulowitz, and Williams (6) suggested that 16cr-hydroxypregnenolone may serve as a precursor of 16cr-hydroxyprogesterone (Reaction f, Fig. 1). We have investigated the relative contributions of Reactions a + e and c + d (Fig. 1) for the synthesis of 17-hydroxyprogesterone in a single incubation of slices of hyperplastic human adrenal cortical tissue with pregnenolone-7a-H3 and progesterone-B